Increase in tumor-associated macrophages after antiangiogenic therapy is associated with poor survival among patients with recurrent glioblastoma.

Abstract:

:Antiangiogenic therapy is associated with increased radiographic responses in glioblastomas, but tumors invariably recur. Because tumor-associated macrophages have been shown to mediate escape from antiangiogenic therapy in preclinical models, we examined the role of macrophages in patients with recurrent glioblastoma. We compared autopsy brain specimens from 20 patients with recurrent glioblastoma who received antiangiogenic treatment and chemoradiation with 8 patients who received chemotherapy and/or radiotherapy without antiangiogenic therapy or no treatment. Tumor-associated macrophages were morphologically and phenotypically analyzed using flow cytometry and immunohistochemistry for CD68, CD14, CD163, and CD11b expression. Flow cytometry showed an increase in macrophages in the antiangiogenic-treated patients. Immunohistochemical analysis demonstrated an increase in CD68+ macrophages in the tumor bulk (P < .01) and infiltrative areas (P = .02) in antiangiogenic-treated patients. We also observed an increase in CD11b+ cells in the tumor bulk (P < .01) and an increase in CD163+ macrophages in infiltrative tumor (P = .02). Of note, an increased number of CD11b+ cells in bulk and infiltrative tumors (P = .05 and P = .05, respectively) correlated with poor overall survival among patients who first received antiangiogenic therapy at recurrence. In summary, recurrent glioblastomas showed an increased infiltration in myeloid populations in the tumor bulk and in the infiltrative regions after antiangiogenic therapy. Higher numbers of CD11b+ cells correlated with poor survival among these patients. These data suggest that tumor-associated macrophages may participate in escape from antiangiogenic therapy and may represent a potential biomarker of resistance and a potential therapeutic target in recurrent glioblastoma.

journal_name

Neuro Oncol

journal_title

Neuro-oncology

authors

Lu-Emerson C,Snuderl M,Kirkpatrick ND,Goveia J,Davidson C,Huang Y,Riedemann L,Taylor J,Ivy P,Duda DG,Ancukiewicz M,Plotkin SR,Chi AS,Gerstner ER,Eichler AF,Dietrich J,Stemmer-Rachamimov AO,Batchelor TT,Jain RK

doi

10.1093/neuonc/not082

subject

Has Abstract

pub_date

2013-08-01 00:00:00

pages

1079-87

issue

8

eissn

1522-8517

issn

1523-5866

pii

not082

journal_volume

15

pub_type

杂志文章
  • The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide.

    abstract:BACKGROUND:Promoter methylation of O(6)-methylguanine-DNA methyltransferase (MGMT) is an important predictive biomarker in glioblastoma. The T variant of the MGMT promoter-enhancer single nucleotide polymorphism (SNP; rs16906252) has been associated with the presence of MGMT promoter methylation in other cancers. We ex...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nov064

    authors: Rapkins RW,Wang F,Nguyen HN,Cloughesy TF,Lai A,Ha W,Nowak AK,Hitchins MP,McDonald KL

    更新日期:2015-12-01 00:00:00

  • Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a Children's Oncology Group phase I study.

    abstract::The purpose of this study was to determine the dose-limiting toxicities, maximum tolerated dose, pharmacokinetics, and intratumor and brain distribution of motexafin gadolinium (MGd) with involved field radiation therapy in children with newly diagnosed intrinsic pontine gliomas. MGd was administered as a 5-min intrav...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2008-043

    authors: Bradley KA,Pollack IF,Reid JM,Adamson PC,Ames MM,Vezina G,Blaney S,Ivy P,Zhou T,Krailo M,Reaman G,Mehta MP,Children's Oncology Group.

    更新日期:2008-10-01 00:00:00

  • Survivorship care planning and implementation in neuro-oncology.

    abstract::Survivorship has become a significant topic within oncologic care. The tools and means by which the provision of survivorship care can be implemented and delivered are in development and are the focus of significant research oncology-wide. These tools and methods include innovations of survivorship care delivery, surv...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noy110

    authors: Leeper H,Milbury K

    更新日期:2018-11-09 00:00:00

  • Late relapse in primary central nervous system lymphoma: clonal persistence.

    abstract::Recurrence of primary central nervous system lymphoma (PCNSL) after initial diagnosis and treatment occurs within 2 years in most patients, and relapse after 5 years is rare. We evaluated late relapse in our PCNSL population. We identified 10 patients from our database of 378 patients (268 achieved a complete response...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor014

    authors: Nayak L,Hedvat C,Rosenblum MK,Abrey LE,DeAngelis LM

    更新日期:2011-05-01 00:00:00

  • A low percentage of metastases in deep brain and temporal lobe structures.

    abstract:BACKGROUND:Whole-brain radiotherapy (WBRT) in patients with brain metastases (BM) is associated with neurocognitive decline. Given its crucial role in learning and memory, efforts to mitigate this toxicity have mostly focused on sparing radiation to the hippocampus. We hypothesized that BM are not evenly distributed ac...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noz023

    authors: Yanagihara TK,McFaline-Figueroa JR,Giacalone NJ,Lee AW,Soni V,Hwang ME,Hsieh KT,Saraf A,Wu CC,Yang D,Wen PY,Ashamalla H,Aizer AA,Wang TJC,Huang RY

    更新日期:2019-05-06 00:00:00

  • Differential patterns of NOTCH1-4 receptor expression are markers of glioma cell differentiation.

    abstract::Background Notch signaling is deregulated in human gliomas and may play a role in their malignancy. However, the role of each Notch receptor in glioma cell differentiation and progression is not clear. We examined the expression pattern of Notch receptors and compared it with differentiation markers in glioma cell lin...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not168

    authors: Dell'albani P,Rodolico M,Pellitteri R,Tricarichi E,Torrisi SA,D'Antoni S,Zappia M,Albanese V,Caltabiano R,Platania N,Aronica E,Catania MV

    更新日期:2014-01-01 00:00:00

  • Dogs are man's best friend: in sickness and in health.

    abstract::With the median survival of 14.6 months following best available standard of care, malignant gliomas (MGs) remain one of the biggest therapeutic challenges of the modern time. Although the last several decades have witnessed tremendous advancement in our understanding of MG and evolution of many successful preclinical...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/now109

    authors: Bentley RT,Ahmed AU,Yanke AB,Cohen-Gadol AA,Dey M

    更新日期:2017-03-01 00:00:00

  • Diffuse intrinsic pontine gliomas-current management and new biologic insights. Is there a glimmer of hope?

    abstract::Diffuse intrinsic pontine glioma (DIPG) has proven to be one of the most challenging of all pediatric cancers. Owing to a historical reticence to obtain tumor tissue for study, and based on an erroneous assumption that the biology of DIPG would mirror that of supratentorial high-grade astrocytomas, innumerable studies...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nox021

    authors: Cohen KJ,Jabado N,Grill J

    更新日期:2017-08-01 00:00:00

  • Assessment and treatment relevance in elderly glioblastoma patients.

    abstract::Glioblastoma (GBM) is the most common malignant primary brain tumor. Its incidence continues to increase in the elderly because the older segment of the population is growing faster than any other age group. Most clinical studies exclude elderly patients, and "standards of care" do not exist for GBM patients aged >70 ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nou063

    authors: Bauchet L,Zouaoui S,Darlix A,Menjot de Champfleur N,Ferreira E,Fabbro M,Kerr C,Taillandier L

    更新日期:2014-11-01 00:00:00

  • Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection.

    abstract:BACKGROUND:While standards for the treatment of newly diagnosed glioblastomas exist, therapeutic regimens for tumor recurrence remain mostly individualized. The role of a surgical resection of recurrent glioblastomas remains largely unclear at present. This study aimed to assess the effect of repeated resection of recu...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1093/neuonc/nov145

    authors: Ringel F,Pape H,Sabel M,Krex D,Bock HC,Misch M,Weyerbrock A,Westermaier T,Senft C,Schucht P,Meyer B,Simon M,SN1 study group.

    更新日期:2016-01-01 00:00:00

  • The clinical value of patient-derived glioblastoma tumorspheres in predicting treatment response.

    abstract:Background:Advances from glioma stemlike cell (GSC) research, though increasing our knowledge of glioblastoma (GBM) biology, do not influence clinical decisions yet. We explored the translational power of GSC-enriched cultures from patient-derived tumorspheres (TS) in predicting treatment response. Methods:The relatio...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/now304

    authors: D'Alessandris QG,Biffoni M,Martini M,Runci D,Buccarelli M,Cenci T,Signore M,Stancato L,Olivi A,De Maria R,Larocca LM,Ricci-Vitiani L,Pallini R

    更新日期:2017-08-01 00:00:00

  • Prognostic awareness, prognostic communication, and cognitive function in patients with malignant glioma.

    abstract:Background:Malignant glioma (MG) is a devastating neuro-oncologic disease with almost invariably poor prognosis. Prognostic awareness (PA) is the awareness of incurable disease and shortened life expectancy (LE). Accurate PA is associated with favorable psychological outcomes at the end of life (EoL) for patients with ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nox117

    authors: Diamond EL,Prigerson HG,Correa DC,Reiner A,Panageas K,Kryza-Lacombe M,Buthorn J,Neil EC,Miller AM,DeAngelis LM,Applebaum AJ

    更新日期:2017-10-19 00:00:00

  • Akt2 and Akt3 play a pivotal role in malignant gliomas.

    abstract::Akt, one of the major downstream effectors of phosphatidylinositol 3-kinase, is hyper-expressed and activated in a variety of cancers including glioblastoma. However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well u...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nop026

    authors: Mure H,Matsuzaki K,Kitazato KT,Mizobuchi Y,Kuwayama K,Kageji T,Nagahiro S

    更新日期:2010-03-01 00:00:00

  • Recursive partitioning analysis of prognostic variables in newly diagnosed anaplastic oligodendroglial tumors.

    abstract:BACKGROUND:Anaplastic oligodendroglial tumors are rare, and median survival varies widely. Analysis of 1p19q deletion is performed commonly and is an important prognostic factor. However, age and other clinical variables also carry prognostic value, and it is unclear how to incorporate them into clinical decision makin...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nou083

    authors: Panageas KS,Reiner AS,Iwamoto FM,Cloughesy TF,Aldape KD,Rivera AL,Eichler AF,Louis DN,Paleologos NA,Fisher BJ,Ashby LS,Cairncross JG,Urgoiti GB,Wen PY,Ligon KL,Schiff D,Robins HI,Rocque BG,Chamberlain MC,Mason WP,

    更新日期:2014-11-01 00:00:00

  • Myeloablative chemotherapy for recurrent aggressive oligodendroglioma.

    abstract::The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving a...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/2.2.114

    authors: Cairncross G,Swinnen L,Bayer R,Rosenfeld S,Salzman D,Paleologos N,Kaminer L,Forsyth P,Stewart D,Peterson K,Hu W,Macdonald D,Ramsay D,Smith A,Oligodendroglioma Study Group.

    更新日期:2000-04-01 00:00:00

  • Co-polysomy of chromosome 1q and 19p predicts worse prognosis in 1p/19q codeleted oligodendroglial tumors: FISH analysis of 148 consecutive cases.

    abstract:BACKGROUND:This study aimed to evaluate the prognostic significance of co-polsomy of chromosome 1q and 19p in 1p/19q codeleted oligodendroglial tumors (ODGs). METHODS:In a series of 148 ODGs with 1p/19q deletion, co-polysomy of 1q and 19p was detected by fluorescence in situ hybridization (FISH). Log-rank analysis and...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not092

    authors: Ren X,Jiang H,Cui X,Cui Y,Ma J,Jiang Z,Sui D,Lin S

    更新日期:2013-09-01 00:00:00

  • Mitochondrial Bax translocation partially mediates synergistic cytotoxicity between histone deacetylase inhibitors and proteasome inhibitors in glioma cells.

    abstract::The effects of combining histone deacetylase (HDAC) inhibitors and proteasome inhibitors were evaluated in both established glioblastoma multiforme (GBM) cell lines and short-term cultures derived from the Mayo Clinic xenograft GBM panel. Coexposure of LBH589 and bortezomib at minimally toxic doses of either drug alon...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2007-063

    authors: Yu C,Friday BB,Yang L,Atadja P,Wigle D,Sarkaria J,Adjei AA

    更新日期:2008-06-01 00:00:00

  • A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool.

    abstract:BACKGROUND:Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is cont...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not218

    authors: Manterola L,Guruceaga E,Gállego Pérez-Larraya J,González-Huarriz M,Jauregui P,Tejada S,Diez-Valle R,Segura V,Samprón N,Barrena C,Ruiz I,Agirre A,Ayuso A,Rodríguez J,González A,Xipell E,Matheu A,López de Munain A,Tuñón

    更新日期:2014-04-01 00:00:00

  • New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach.

    abstract::Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a "wait and see" policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associa...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nou153

    authors: Duffau H,Taillandier L

    更新日期:2015-03-01 00:00:00

  • Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing.

    abstract:BACKGROUND:Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Mos...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not015

    authors: Agarwal S,Sharma MC,Jha P,Pathak P,Suri V,Sarkar C,Chosdol K,Suri A,Kale SS,Mahapatra AK,Jha P

    更新日期:2013-06-01 00:00:00

  • Altered brain morphology after focal radiation reveals impact of off-target effects: implications for white matter development and neurogenesis.

    abstract:Background:Children with brain tumors treated with cranial radiation therapy (RT) often exhibit cognitive late effects, commonly associated with reduced white matter (WM) volume and decreased neurogenesis. The impact of radiation damage in particular regions or tissues on brain development as a whole has not been eluci...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nox211

    authors: Beera KG,Li YQ,Dazai J,Stewart J,Egan S,Ahmed M,Wong CS,Jaffray DA,Nieman BJ

    更新日期:2018-05-18 00:00:00

  • Gene expression analyses of grade II gliomas and identification of rPTPbeta/zeta as a candidate oligodendroglioma marker.

    abstract::Grade II gliomas are morphologically and clinically heterogeneous tumors for which histopathological typing remains the major tool for clinical classification. To what extent the major histological subtypes - astrocytomas, oligodendrogliomas, and oligoastrocytomas - constitute true biological entities is largely unres...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2007-041

    authors: Hägerstrand D,Smits A,Eriksson A,Sigurdardottir S,Olofsson T,Hartman M,Nistér M,Kalimo H,Ostman A

    更新日期:2008-02-01 00:00:00

  • Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1.

    abstract::People with neurofibromatosis 1 (NF1) have multiple benign neurofibromas and a 10% lifetime risk of developing malignant peripheral nerve sheath tumors (MPNSTs). Most MPNSTs develop from benign plexiform neurofibromas, so the burden of benign tumors may be a risk factor for developing MPNST. We studied 13 NF1 patients...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2008-011

    authors: Mautner VF,Asuagbor FA,Dombi E,Fünsterer C,Kluwe L,Wenzel R,Widemann BC,Friedman JM

    更新日期:2008-08-01 00:00:00

  • Global incidence of malignant brain and other central nervous system tumors by histology, 2003-2007.

    abstract:Background:Previous reports have shown that overall incidence of malignant brain and other central nervous system (CNS) tumors varied significantly by country. The aim of this study was to estimate histology-specific incidence rates by global region and assess incidence variation by histology and age. Methods:Using da...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nox091

    authors: Leece R,Xu J,Ostrom QT,Chen Y,Kruchko C,Barnholtz-Sloan JS

    更新日期:2017-10-19 00:00:00

  • Homeobox C9 suppresses Beclin1-mediated autophagy in glioblastoma by directly inhibiting the transcription of death-associated protein kinase 1.

    abstract:BACKGROUND:The transcription factor homeobox C9 (HOXC9) plays a crucial role in developmental regulatory systems, where it determines the specific positional identities of cells along the anteroposterior axis. The expression of HOXC9 has been found to be dysregulated in some cancers such as lung cancer, breast cancer, ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nov281

    authors: Xuan F,Huang M,Liu W,Ding H,Yang L,Cui H

    更新日期:2016-06-01 00:00:00

  • Adoptive transfer of genetically modified Wilms' tumor 1-specific T cells in a novel malignant skull base meningioma model.

    abstract:BACKGROUND:Meningiomas are the most commonly diagnosed primary intracranial neoplasms. Despite significant advances in modern therapies, the management of malignant meningioma and skull base meningioma remains a challenge. Thus, the development of new treatment modalities is urgently needed for these difficult-to-treat...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not007

    authors: Iwami K,Natsume A,Ohno M,Ikeda H,Mineno J,Nukaya I,Okamoto S,Fujiwara H,Yasukawa M,Shiku H,Wakabayashi T

    更新日期:2013-06-01 00:00:00

  • Telomere maintenance and the etiology of adult glioma.

    abstract::A growing body of epidemiologic and tumor genomic research has identified an important role for telomere maintenance in glioma susceptibility, initiation, and prognosis. Telomere length has long been investigated in relation to cancer, but whether longer or shorter telomere length might be associated with glioma risk ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nov082

    authors: Walsh KM,Wiencke JK,Lachance DH,Wiemels JL,Molinaro AM,Eckel-Passow JE,Jenkins RB,Wrensch MR

    更新日期:2015-11-01 00:00:00

  • Regulation of bioenergetics through dual inhibition of aldehyde dehydrogenase and mitochondrial complex I suppresses glioblastoma tumorspheres.

    abstract:Background:Targeted approaches for treating glioblastoma (GBM) attempted to date have consistently failed, highlighting the imperative for treatment strategies that operate on different mechanistic principles. Bioenergetics deprivation has emerged as an effective therapeutic approach for various tumors. We have previou...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nox243

    authors: Park J,Shim JK,Kang JH,Choi J,Chang JH,Kim SY,Kang SG

    更新日期:2018-06-18 00:00:00

  • Challenges to targeting epidermal growth factor receptor in glioblastoma: escape mechanisms and combinatorial treatment strategies.

    abstract::Epidermal growth factor receptor (EGFR) gene amplification and activating mutations are common findings in glioblastomas. EGFR is at the top of a downstream signaling cascade that regulates important characteristics of glioblastoma cells, including cellular proliferation, migration, and survival. Targeting EGFR has th...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nou222

    authors: Roth P,Weller M

    更新日期:2014-10-01 00:00:00

  • Variation over time and interdependence between disease progression and death among patients with glioblastoma on RTOG 0525.

    abstract:BACKGROUND:We assessed the longitudinal hazard characteristics for death and progression in patients with glioblastoma, evaluated the impact of prognostic factors and treatment on the hazard within different time intervals to determine if effects are time varying, and quantified the influence of progression on survival...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,随机对照试验

    doi:10.1093/neuonc/nov009

    authors: Wang M,Dignam JJ,Won M,Curran W,Mehta M,Gilbert MR

    更新日期:2015-07-01 00:00:00